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. 2018 Oct 12;68(7):1259–1270. doi: 10.1136/gutjnl-2017-315490

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© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Heterozygous Arid1a loss in acinar cells accelerates pancreatic intraepithelial neoplasia (PanIN) formation and shortens survival. (A) After tamoxifen, tomato expression in Ptf1a^CreER; ROSA26-LSL-tdTomato (Td) mice was restricted to acinar cells. None was seen in islets (yellow dashed outline) or ducts (yellow arrowheads). (B) After tamoxifen, ARID1A expression was lost in acinar cells but retained in duct and islet cells in Ptf1a^CreER; Arid1a^f/f mice. (C) After tamoxifen, Kras^G12D; Ptf1a^CreER; Arid1a^+/+, Arid1a^f/+ and Arid1a^f/f mice all developed PanIN. (D) PanIN in Kras^G12D; Ptf1a^CreER; Arid1a^f/f mice did not express ARID1A. (E) Kras^G12D; Ptf1a^CreER; Arid1a^f/+ formed more PanIN, n=9 for each group, *P<0.05. (F) Kras^G12D; Trp53^f/+; Ptf1a^CreER; Arid1a^f/+ mice had worse survival than Kras^G12D; Trp53^f/+; Ptf1a^CreER; Arid1a^+/+ mice. *P<0.05. (G) Kras^G12D; Trp53^f/+; Ptf1a^CreER mice with heterozygous and homozygous Arid1a loss developed components of undifferentiated pancreatic ductal adenocarcinoma with rhabdoid or sarcomatoid features.